Monkeypox treatment options: current status of antiviral drugs – a correspondence
Authors: Dhanraj Ganapthy, Saravanan Sekaran, Suresh Kumar Rajamani Sekar
Journal: International Journal of Surgery (2023)

Dear Editor, At the time of writing this letter, according to Centers for Disease Control and Prevention, a total of 82,474 monkeypox virus-infected cases were reported in 110 countries across the globe. There are no particular therapies for monkeypox. However, since the viruses that cause monkeypox and smallpox are so similar, antiviral medications designed to guard against smallpox may be beneficial in treating monkeypox. Animal studies suggest that certain antivirals, originally developed for the treatment of smallpox, may also be useful against monkeypox. Although human dose–response trials have been performed, the effectiveness of the medications remains unclear1. We take the liberty of enlightening the readers on the currently used antiviral agents in the management of monkeypox. Brincidofovir and cidofovir Brincidofovir has been used to treat smallpox in the United States since June 2021. Brincidofovir (oral) is a drug that is similar to cidofovir (intravenous), but it may have a better safety profile due to less renal toxicity2. These drugs work by inhibiting the viral DNA polymerase3. Animal studies on the efficacy of brincidofovir in the treatment of monkeypox infections are limited, although the drug has been found to be successful against other orthopoxvirus infections4. Although there is currently no human clinical evidence on the effectiveness of cidofovir against monkeypox, it has been shown to be active and effective in vitro against deadly monkeypox virus infections in animals5. Cidofovir must be administered together with intravenous normal saline and probenecid treatment. Due to the potential for brincidofovir to raise serum transaminases and serum bilirubin, liver function tests should be performed before and periodically during therapy. Tecovirimat The first antiviral medication approved for the treatment of smallpox in adults and pediatric patients weighing at least 3 kg, tecovirimat (also known as TPOXX or ST-246) is the drug of choice6. Dual treatment with tecovirimat and brincidofovir may be utilized in individuals with advanced illness. Tecovirimat prevents the propagation of the virus within an infected host by blocking the virion protein VP37, which is responsible for the last stages of viral development and release from the infected cell7. Animal studies have shown that tecovirimat increases survival from deadly monkeypox virus infections relative to placebo-treated animals during various stages of illness; however, the drug's effectiveness against monkeypox in people has not been studied8. A larger safety trial with 359 human volunteers found that the placebo side-effect profile was rather comparable to that of tecovirimat9. Patients suffering side effects from the smallpox vaccination, such as eczema vaccinatum and developing vaccinia, were given tecovirimat in conjunction with exhibiting vaccinia immune globulin (VIG) in a few trials6. When treating non-variola orthopoxvirus infections like monkeypox, tecovirimat may be used thanks to the Centers for Disease Control and Prevention's Emergency Access Investigational New Protocol. The protocol also allows for the oral capsule's contents to be opened and mixed with fluid or a soft diet for patients under 13 kg. Tecovirimat may be taken by mouth as a capsule or injected into the veins10. VIG Hyperimmune globulin (VIG) has been approved by the US Food and Drug Administration for use in treating vaccinia vaccination-related side effects. Vaccinia virus may cause a variety of abnormal illnesses, such as eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, vaccinia infections in people with skin disorders, and vaccinia infections in healthy persons except for ocular infections11. While VIG has shown promise as a cure for both monkeypox and smallpox, there is a dearth of evidence on its efficacy and no human trials of its usage for either disease. Those with extreme immunodeficiency in T-cell function should not get the vaccinia virus vaccine; however, patients with a history of exposure may be administered VIG instead. An Investigational New Drug application is necessary for VIG treatment12. The treatment for monkeypox may rely on a variety of factors, including prior vaccination conditions, initial overall health, and simultaneous illnesses or comorbidities; however, for many people infected with the monkeypox virus, the disease course is mild and self-limiting, even within the lack of specific therapy. Thus, it seems that the most acceptable technique is to design individualized medicines based on each person's risk of acquiring serious diseases. Ethical approval None. Sources of funding None. Author contribution S.S., D.G., and S.K.R.S. devised the concept, performed the literature search, and drafted the letter. Conflicts of interest disclosure There are no conflicts of interest. Research registration unique identifying number (UIN) None. Guarantor The submission is a correspondence. No new study was performed. All authors accept full responsibility for the submitted letter. Data availability The correspondence is based exclusively on resources that are publicly available on the internet and duly cited in the 'References' section. No primary data were generated and reported in this manuscript. Therefore, data has not become available to any academic repository.